Part Ⅰ. Asymmetric anti-Aldol Reaction of Unsubstituted Cyclobutanone Utilizing Chiral N-Amino Cyclic Carbamate Auxiliary and Lanthanum Additive Part Ⅱ. Study on Pyridine-Boryl Radical-Promoted Pinacol Coupling and Aza-Pinacol Coupling

Abstract

Part Ⅰ. Asymmetric aldol reaction is recognized as an efficient synthetic method for the construction of a carbon-carbon bond containing up to two stereogenic centers. Many successful studies have been accomplished, but unsubstituted cyclobutanone has rarely been examined despite its synthetic and medicinal importance. Herein, stereoselective aldol reaction of unsubstituted cyclobutanone is conducted by utilizing N-amino cyclic carbamate auxiliary and lanthanum additive. The anti-aldol product was obtained in excellent stereoselectivity, and the use of a stoichiometric amount of lanthanum additive is critical for stereocontrol. The reproducibility was ensured by quenching the reaction mixture at a low temperature. Auxiliary removal was accomplished without compromising the stereochemical integrity by using phosphoric acid.

Part Ⅱ. Previously by our group, a metal-free, persistent boryl radical-promoted pinacol coupling was reported. This method exhibited excellent efficiency in the coupling of diary ketones. However, a moderate yield was obtained in the coupling of aromatic aldehydes. Thus, reaction condition optimization was performed. Increasing the reaction temperature was the most efficient solution for improving the yield. In addition, aza-pinacol coupling was probed as a ketyl radical application method by employing stoichiometric imine derivatives as radical acceptors. However, the dimerization of imines proceeds predominantly. Even when benzophenone was employed instead for fast ketyl radical generation, the amount of 1,2-diols was not negligible.